Altered neural activation in ornithine transcarbamylase deficiency during executive cognition: an fMRI study.

BACKGROUND: Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder characterized by hyperammonemia resulting in white matter injury and impairments in working memory and executive cognition. OBJECTIVE: To test for differences in BOLD signal activation between subjects with OTCD and healthy controls during a working memory task. DESIGN, SETTING AND PATIENTS: Nineteen subjects with OTCD and 21 healthy controls participated in a case-control, IRB-approved study at Georgetown University Medical Center. INTERVENTION: An N-back working memory task was performed in a block design using 3T functional magnetic resonance imaging. RESULTS: In subjects with OTCD we observed increased BOLD signal in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) relative to healthy age matched controls. CONCLUSIONS: Increased neuronal activation in OTCD subjects despite equivalent task performance points to sub-optimal activation of the working memory network in these subjects, most likely reflecting damage caused by hyperammonemic events. These increases directly relate to our previous finding of reduced frontal white matter integrity in the superior extents of the corpus callosum; key hemispheric connections for these areas. Future studies using higher cognitive load are required to further characterize these effects.

High-capacity spatial contextual memory.

Humans show implicit memory for complex spatial layouts, which aids in subsequent processing of these layouts. Research efforts in the past 5 years have focused primarily on a single session of training involving a dozen repeated displays. Yet every day, people encounter many more visual layouts than were presented in such experiments. In this study, we trained subjects to learn 60 repeated displays, randomly intermixed within 1,800 nonrepeated displays, spread over 5 consecutive days. On each day, the subjects conducted visual search on 360 new displays and a new set of 12 repeated displays, each repeated 30 times. Contextual memory was observed daily. One week after the fifth session, the subjects still searched faster on the repeated displays learned previously. We conclude that the visual system has a high capacity for learning and retaining repeated spatial context, an ability that may compensate for our severe limitations in visual attention and working memory.